Preparation of steroid alcohols from steroid aldehydes



Patented Ma 1, 1951 UNITED STATES PATENT OFFICE PREPARATION OF STEROIDALCOHOLS FROM STEROID ALDEHYDES Robert H. Levin, A. Von McIntosh, Jr.and George Br Spero, Kalamazoo, Mich., assignors to The Upjohn CompanyKalan'iazoo, Mich, a

corporation of Michigan No Drawing; Application 'Qctober 2, 1947, SerialN0.-777, 578

9 Claims. ((11.260-3975) wherein P represents a pregnane nucleus attached tothe side-chain at the 20position, and n is selected from zero,one, and two, and with a method for the preparationthereof: from-steroidaldehydes of the formula:

wherein P and n have the values given for the desired alcohol.

It is an objectof the presentinvention to pro- Vide novel primarysteroid alcohols containing thepregnane nucleus and having a side-chainat the-20 position. These novel alcohols, con-'- taining acyloxy groupsin the pregnane nucleus, have been unobtainable previously, as previousmethods of alcohol preparation have involved the concomitantsaponification or hydrolysis of the nuclear acyloxy groups. A; furtherobject of the invention is the provision of a process for theproductionof the said'alcohols from steroid alde hydes having aside-chain containing the same number of carbon atoms. Other objectsofthe invention will-become apparent hereinafter.

Members of the-new g'roupof'compounds have been prepared, isolated, andfound to be valuable intermediates in the-preparation of more complexorganic molecules, including certain hormones.

Among the steroid 'aldehydes which may be employed as suitable. startingmaterialsfor the preparation of the steroid alcohols are cholanals,cholenals, lithocholals, d'escic-ycholals, cholals,

2 tetrahydroxy cholals, and similar steroid sidechain aldehydes havingthe C-'20 side-chain previouslygiven, Likewise, other aldehydes ofunsaturated steroids, such as 3-hydroxy-(delta 5) cholenic,3,11'-dihydroxy-(delta- 5) -cholenic, and

3-hydroxy-(delta 5,-7)-choladienic aldehydes, are suitable startingmaterials.

Other suitable aldehydes are those having one less side-chain carbonatom", i. e., the" nor-cholanals and related compounds havingsubstituents as given above in the cholenic series. The bisnorcholanalshave two less carbon atoms in the sidechain, and these compounds. arealso suitable starting materials.

Aldehydes having the designated side-chains and. additional substituentsin the nucleus, suchashydroxyl groups, esters andether derivatives ofhydroxyl groups, double bonds, protected double bonds, e. g., asbyconversion to the dihalide' or hydrohalide, and halogen atoms may alsobe used as starting materials. Some compounds having the mentionedsubstituents'have been indicated for the first series, but any compoundhaving the; prescribed pregnane nucleus and the specified side-chain,regardless of other nuclear substitdures, both of which proceed throughthe acid,

3 4 chloride. The first (A) involves reaction or the 1941, 331 The aciddissolved within five acid halide brOmide ch h a utes and the solutionwas allowed to stand, with captain n Py d t e 88001111 nvolvesoccasional swirling, at room temperature for one reaction of the acidchloride with a suspension hour. Twenty milliliters of a 1:1 mixture ofanof lead mercaptide in ether according to the folhydrous benzene andether was then added and lowing sequence, as illustrated for anunsubsti= the whole evaporated to dryness in vacuo at 40 tuted acid:degrees centigrade. This process of treatment on, on, 0 0H, 0 m0H-(CH:)COOH 11,0 c irroHnl-t -oi 11,0 (EH-(CHfl-Hl-SR H10 H5O A H3Oso=o1 RSH(pyrldine) or or Pb (SR): 00,01 (other wherein n is zero, one,or two; and R is an alcohol with benzene-ether was repeated twice toensure residue, preferably a hydrocarbon radical. Both complete removalof excess thionyl chloride.

of the given procedures have proven suitable. To the resulting acidchloride dissolved in 10 Choice of the R radical in the startingthioester milliliters of anhydrous benzene was added 0.4

is purely arbitrary, the availability of the mermilliliter (0.005 mole)of dry pyridine and 2 captan or lead mercaptide being the only limitingmilliliters (1.12 grams, 0.009 mole) of benzyl merfactor. B may thus bealkyl, e. g., methyl, ethyl, captan, a precipitate soon forming. Afterstandpropyl, isopropyl, butyl, isobutyl, amyl, n-octyl, ing fortwenty-four hours at room temperature, or the like; cycloalkyl, e., g.,cyclopentyl, cyclothe mixture was diluted with 15 milliliters of hexyl;c cloalkylalkyl, g, cyclohexylmethy]; water and 15 milliliters of ether,whereafter the aryl, g, h l, naphthyl; or aralkyl; e, g precipitatedissolved and the ether-benzene phase benzyl or phenethyl. Unsaturatedaliphatics and was eparated. The organic portion was excy loaljphaticmay 21180 be employed as 11 tracted with two l5-milliliter portions ofwater, as compounds wherein R is chloroethyl, nitroone Per sPdlumhydroxide, cent? phenyl, aminopropyl' bromonaphthyl and the hydrochloricacid and finally again with water.- like, provided the required startingmaterial is The neutral fraction was dried over anhydrous availablesodium sulfate, the solvent evaporated to dryness in vacuo, and theresidual oil crystallized from 50' Procedure A.-Mercwptan in pyridinemilliliters of 95 per cent alcohol to give 1.38 grams (73 per cent) ofproduct, M. P. 147-152 degrees centigrade. After threerecrystallizations from 40 alcohol, 1.23 grams (65.5 per cent) of thebenzyl thioester with a constant melting point of Equimolar proportionsare satisfactory. but an excess of mercantan may snmptimeg be 154-156degrees centlgrade (corn) was obtained.

ployed to advantage. Gentle heating sometimes Efmmple 2 1/lz-lllpha-diformoly- The acid chloride. usually in an or anic solvent.such as anhvdrous benzene. is admixed ith a selected mercantan in aridine solution.

increases reaction rate, but is not usually thiocholmate necessary. asthe reaction occurs readily at room The acid chloride (prepared from 4.5grams tem erature. The reaction product may be (0.01 mole) of 3-alpha,12-alpha-diformoxydesworked up with water and ether. aoueousooroxycholic acid in themanner describedin Example tions extracted andthe combin d ether layer 1) was dissolved in 30 milliliters of anhydrouswashed with water, dilute alkali. dilute acid. and ether and added to1.8 grams (0.0055 mole) of lead again with water. After dryin theneutral fracethyl mercaptide covered with 20 milliliters of antion andevaporating solvent. the residual oil may hydrous ether. The mixture wasallowed to stand be crystallized from a suitable solvent. e. g.. alcoatroom temperature with occasional swirling, hol, to yield the desiredthioester, usually a stable the yellow lead mercaptide being graduallyresolid. placed by white lead chloride. After twenty-four hours, thesolution was filtered and the precipi- 006111 e mercaptide in ether tatewashed with 50 milliliters of ether. The

The acid chloride in anhydrous ether is added ed ether filtrate WasWashed with 100 to a mixture of ether and selected leadmercapmilliliters of one per cent sodium hydroxide and tide, or viceversa. Equimolar proportions are 300 milliliters of Water, then driedOver ysatisfactory; other ratios may be used if desired. drOilS SodiumSulfate and evaporated to dryness The reaction mixture is allowed tostand with in vacuo n e Steam at he residual Oil occasional swirling,gentle heating if d i d, was dissolved in 50 milliliters of hot alcoholand The reaction product may b orked up as i 10 milliliters of wateradded. On cooling, an oil Procedure A. separated, taking with it all thecolor in the The following examples are given to illustrate solution,after which crystallization yielded 2.2 the preparation of a suitablestarting thioester, grams of materialn a o al gram of but are in no wayto b construed as limiting crystals was obtained by crystallizing theoil from alcohol, the total yield being 2.52 grams (51 per Example1.Benzyl 3-alpha,IZ-aZpha-dzacetoxycent of the theoretical), M. P.105-110 degrees "opthwcholanate centigrade. After threerecrystallizations, the

T 15 grams 0 0033 mole) f 3 a1Dha,12 melting point was constant at111-112 degreesalpha diacetoxy-nor-cholanic acid was added 6 Centigrade(con?) milliliters (9.8 grams, 0.082 mole) of purified thi- Othersuitable o sters which may be emonyl chloride (Fi r, Experiments inOrganic ployed as starting materials in the method of the- Chemistry,Part II, Heath and C0,, New YQrk 75. present invention are given in thetable.

TA'BliE- ESTERs OF STEROID ACIDS Analyses, per cent R 2 \al Gompound M-P" -3 ggfiga g gi ggg Carbon Hydrogen Sulfur 'Calcd Found Galcd. FoundCalcd. Found ethyl3-beta=hydroxy-(delta )-thiocholenate 108: 540955 -38.5 CzeHnOzS... 74. 59 74. 64 10. 00 10. 07 7.66 7. 79 ethyl 3-.betaformoxy-fdelta.5)thiocholenate 81-82 72. 60 72. 07 9. 48 9. 61 7. 18 7.01 ethyl3=betznacetoxy-(delta 5),-thioeholenate 101,5-1035 .99 72.929.63 9.69 6.98 7.36 isopropyllw-beta-acetoxy-(delta5)-thiocholenate131433 37 73. 39 9. 77 9. 55 6; 75 6. 81 tertgbutyl3-beta-ocetoxy-(delta 5)-ith1ocholcn- .109.5.l7l .72 74.07 9.90 9.960.56 '6. 71

..a e. n-hexyl-3-beta-acctoxy-(delta 5) -thiocholenate. 77. 5-79. 5C32H52O3S 74. 37 74. 70 10. 14 10. 00 6. 6. 60 ethyl-3-chloro-(delta5)-thiocl1olenate 103.-5-105 CztHnQSCl. .7144 71. 51 9. 46 9. 58 8. ll 48. 75 ethyl-3-beta-acetoxy-5-chloronor-thiocholanate. 165-168C28H4303SCL 6. 45 6. 32 ethyl 3-beta-acetoxy-(delta'5)ebisnor-thiochol-132.'l33 CZGHJOOSS...... 72.18 72.50 9.32 9.13 7. 41 7. 44

on e. ethyl 3-alpha,12-diformoxy 3 thiocholanate 11lill2 CzsHuOaS 3 ..9.00 8. 89 0. 51 6. 51 ethyl 3-alpha-iormoxy .thiocholanate l 81:820211144038. 72. 27 72. 53 9. 89 9. 74 7. l4 7. 23 ethyl3-a1pha,lZ-diacetoxymoiithiocholanate '91-91. 5 C2uH4605S 08. 76 69. 079. 15 9. 47 6. 33 6. 37 benzy3a1pha,12-alpha-diacetoxy-nor thicehol-154'-l56 Ca4H4sOaS 71. 79 7,1. 56 i 8; 51 8. 79 5. 64 5.66

:ana e. pheiilyl l t'3-alpha,l2-alpha diacetoxyilor-thio- 146-147OaaHieO5S. 71. 44 71. 8. 36 8.04 5. 78 5. 64

c o ana e. phenyl 3=bcta-acetoxy-(delta 5)-thiooholenate- 1 28. 5-130-n. 75. 75. 11 8. 8. 59 6. 29 6. 89 benzyl 3-b'eta-acetoxy-(dclta5)thiocholenate 85-86: 5 75. 67 75. 77 9. 05 8. 72 ethyl3-alpha,7-alpha, IZ-alpha-triformoxythioc. 128 165. 78 8. 44 8. 07

cholanate. ethyl 3-alpha-hydroxy-12-alpha-acetoxythio- 9. 54 9. 34

. cholanate. ethyl 3-methoxy-(delta 5)-bisnor-thiocholenate 94-96ethyl3=benzoyloxy-(delta 5)-thiocholenote l78-l82 ethyl thiodehydrocholatc s. 244246. 5

1 All M. -P.s corrected.

Rotations taken at approximately 25 C. in chloroform with a 1 cm. tube.5 Desoxycholic acid is formulated as 3-alpha-12-alpha, according to thelatest evidence (Ann. Rev. Biochem. 15, 16211946).

4 Chlorine analysis.

"The-presence or absence'of substituents in the pregnane nucleus of thethioester, such as hydroxy,=ester or ether groups convertible to hydroxywith the aid of hydrolysis, halogen, double bonds,'and the like,'isimmaterial tothe present process, as it has been found that sensitivegroups commonly present in the steroid nucleus are stable under theconditions of reaction. The stability, particularly that of a nucleardouble bond, is of considerable value, as any double bonds do notrequire protection during preparation or the aldehydefrom" thethioester.

'Desulfurization' agents which may be employed to prepare steroidaldehydes from thioesters include modified Raney nickel catalysts,modified Raney iron catalysts, and other modified catalysts of thistype. Preparation ofYRaney-type catalysts is known to the art (R.Pauland G. Hilley, Comp.,rendus, 206, 608'.(1938) ;.U. S.Patent..2,366,311 to F. W. Breuer; .HomerAdkins, Reactions of Hydrogenwith Organic Compounds over Coppers-Chromium Qxide land NickelCatalysts, University :of Wisconsin- Press,-.Madi son, 1937 1 (p. 20)).If such .inorma lly 'iactive Raney type catalysts are employed, however,the desired aldehydes are not'produced. It has now been found that, uponproper modification, a Haney-type catalyst is an effective agent forsplitting 'C-S bonds and replacing them with 0-H bonds, and thussuitable for use-in the conversion of' steroid thioesters tosteroidaldehydes in high yields. Such modification may be accomplished byallowing the'Raney-type catalyst to age considerably, orby treatinanormally active Raney-type catalyst with .a [hydrogen acceptor, e. g.,.an ethylene, or a. carbonyl compound such as a ketone. oran aldehyde.This treatment may be advantageously carried out by refluxingthenormally activecatalyst with .the hydrogen acceptor ,totmodify. thecatalyst sufficiently, usually for a period of an hour or more,depending ;uponiniti'al catalyst activity, ratios. of

catalyst to hydrogen acceptor, et cetera. The modified Raney-typecompositions will desulfurize, that is convert .a C-S bond to a (3-Hbond, ;but dov not reduce carbonyl groups orethylenic linkages-yinthecompounds treated .or productsproduced. This isbecause themodification, i.--e., reaction :with a hydrogen acceptor, apparentlyremoves adsorbed hydrogen from the surfaces of theRaney-typecomposition, or, for some other unknown-reason, eliminates the reducingactivity of the normally active Haney-type catalysts. ,Acetonehas beenfound especially suitable for modification of the Raney-type-catalyst,which, .for purposes of convenience, is usually Haney-nickel. Any othersuitable hydrogen acceptor -or 'Raney-type catalyst may also beemployed, however.

The desulfurization is conducted conveniently by mixing together themodified Raney-type catalyst and a sclected'steroid thioester. Thereactants. are maintained in contact for a period of time .sufiicient toproduce. .desulfurization. of the starting thioester, with production.of the corresponding,sideechain-length aldehyde. Agitation is desirableforintimatecontact of reactants, and heating is likewise advantageous insome instances. The temperature is ordinarily maintained between about15 degrees centigrade and degrees centigrade. Common organic solvents,such as acetone, alcohol, ether, and the like, or any-organic solvent inwhich the thioester is soluble and-stable, may be employed. Likewise,water, or mixtures of water and an organic solvent, are suitable media,providing efficient contact of reactants is maintained. Productseparation is accomplished by removing thedesulfurizing agent andworking up the orgame 7 product according to conventional procedure.

The preparation of the. steroid .aldehyde from asteroid thioester. maybe illustrated by thef'ollowing sequence wherein a simple unsubstitutedsteroid nucleus is shown:

3 H3O -WEh--BR H 0 desulfurization If desired, characterization of thealdehyde may be readily accomplished by formation of an aldehydederivative such as the oxime, semicarbazone, or other well knownaldehyde derivatives.

The preparation of an aldehyde by desulfurization of the thioester isdescribed in detail in the following illustrative examples, which,however, are not to be construed as limiting.

Example 3.-3,12-diacetoazy-nor-cholanal-23 A suspension of 10 grams ofRaney nickel in 3) milliliters of acetone was heated under reflux fortwo hours, whereafter one gram of ethyl 3,12-diacetoxy-nor-thiocholanate in 20 milliliters of acetone, followed by 20milliliters of water, was added thereto. The mixture was heated underreflux for 70 minutes, then cooled, filtered to remove Raney nickel, andconcentrated in vacuo. The residue was extracted with ether, the ethersolution washed with dilute acid, dilute alkali, and water, after whichsolvents were removed. The residue was treated with semicarbazideacetate to give 0.71 gram of the semicarbazone of3,12-diacetoxy-nor-cholanal-23, M. P. 210-226 degrees centigrade. Asample recrystallized several times melted at 229-2305 degreescentigrade.

Example 4.-3-formaZ-ZithocholanaZ-24 One gram of ethyl3-formyl-thiolithocholate was reduced to the aldehyde and isolated asthe semicarbazone as described above. The yield of crude semicarbazone,M. P. 182-189 degrees centigrade, was 0.96 gram. After twocrystallizations from toluene and methanol, 032 gram, melting at215-2165 degrees centigrade, remained.

Anal. Calcd.: C, 70.07; H, 9.73; N, 9.43 Found: C, 70.37; H, 9.76; N,9.60

The sample melting at 215-216 degrees centigrade was suspended in ether,washed with water, and recrystallized to give a sample melting at224-227 degrees.

Eaample 5.3-beta-acetomy-(delta -bz'snor-' cholenaldehyde A suspensionof 5 grams of Raney nickel in 15 milliliters of acetone was heated underreflux for 2 hours, then 0.50 gram of ethyl 3-betaacetoxy-(delta5)-bisnor-thiocholenate in milliliters of acetone and 8 milliliters ofwater was added. The mixture was refluxed for two hours, allowed to coolslightly, and filtered to remove Raney nickel. The nickel was washedwith methanol. Crystals began separating in the filtrate, which wasplaced in the refrigerator for three days; the crystals were thenseparated by filtration. The filtrate was diluted with water, giving 197milligrams of amorphous powder; M. P. 88-90 degrees centigrade. Theamorphous powder (197 milligrams), 0.20 gram of semicarbazidehydrochloride, 0.3 gram of sodium acetate, 8 milliliters of absoluteethanol, and 2.5 milliliters of water were heated under reflux for 2hours, the reaction mixture cooled and diluted with water to give 246milligrams of crystals; M. P. 190-200 degrees centigrade.crystallizations from per cent alcohol and water, the melting point roseto 215-218 degrees centigrade.

Anal. Calcd. for C25H3803N32 N, 9.805

Found: N, 9.70.

The powder, M. P. 88-90 degrees centigrade, was 3-beta-acetoxy-(delta 5)-bisnor-cho1enaldehyde, which upon recrystallization melted at 101-108degrees centigrade.

Reduction of the aldehyde to an alcohol of the.

formula:

P( CH2) n-CH2OH wherein P and n have the values previously assigned, maybe carried out with any suitable Raney-type hydrogenation catalyst.Among the Raney-type catalysts which may be mentioned are Raney nickeland Raney iron. Superactivated catalysts are available, and employmentof such catalysts of enhanced activity is sometimes advantageous. Anorganic solvent, such as ether, alcohol, benzene, toluene, or ethylacetate are suitable. The reaction is conducted by admixing thereactants in the presence of a solvent, and temperatures between aboutzero and about degrees centigrade are preferred. The product may beremoved from the reaction vessel after completion of the reaction,separated from Haney-type catalyst, and then worked up for purificationand separation purposes as desired, usually by direct crystallizationfrom the solvent employed.

The following examples are given to illustrate the preparation of theprimary alcohols from aldehydes, but are in no way to be construed aslimiting.

Example 6.-Reduction of 3-beta-acetory-bisnor- (delta 5) -ch0lenaldehyde3 beta acetoxy-( delta 5) -bisnor-cholenaldehyde (prepared from ethylS-beta-acetoxy-(delta 5)-bisnor-thiocholenate by desulfurization withmodified Raney nickel) was used for preparation of3-beta-acetoxy-ZZ-hydroxy-(delta 5) bisnorcholene. The sample usedmelted at 90-100 degrees centrigrade, and contained at least 61 per centof aldehyde as shown by assay with dinitrophenylhydrazine.

A suspension of 222.6 milligrams of the crude aldehyde in 18 millilitersof absolute alcohol was stirred with 2.0 grams of Wisconsin Raney nickelat room temperature for 30 minutes, the nickel was removed by filtrationand washed with three 5-milliliter portions of hot acetone. The filtrateand washings were combined and boiled down to about 20 milliliters, thendiluted while hot with 14 milliliters of water. The clear solution gaveneedle-shaped crystals on cooling. The yield was 185.7 milligrams of3-beta-acetoxy-22-hydroxy- (delta 5)-bisnor-cholene; M. P., 152 degreescentigrade.

Example 7.-Reclaction of 3,12-dzacetomy-norclwZanal-23 Crude ethyl3,12-diacetoxy-nor-cholanal-23 (prepared by desulfurization of 'ethyl3-alpha-l2- After severalalpha-diacetoxy-nor-thiocholanate with modifiedRaney nickel) is reduced according to the procedure of Example 6 to givean excellent yield of 3-alpha-l2-alpha-diacetoxy-g3-hydroxy norcholane,M. P. 154-155 degrees centigrade.

Example 8.Reduction of 3-beta-acetomy-(delta 5) -choZenaZ-24 Thealdehyde (prepared by desulfurization of ethyl 3-beta-acetoxy-(delta 5)thiocholenate with modified Raney nickel) is reduced in the same manneras given for Example 6 to produce 3-beta-acetoxy-24- hydroxy (delta 5')cholene, M. P. 143.5-146 degrees centigrade.

An advantage of the process as previously outlined is the possibility ofreducing a steroid aldehyde, having the selected side-chain length, to aprimary alcohol of corresponding side-chain length, without convertingnuclear acyloxy groups to hydroxy groups. For example, starting with a3,12-diacy1oxy pregnane derivative of designated side-chain length, thereduction converts the aldehyde group to a primary alcohol group withoutafiecting the acyloxy group. However, when one or both acyloxy groupsare formoxy, prolongation of the reaction period may be employed, ifdesired, to obtain conversion of the formoxy group at position 3 to ahydroxy group. The conversion of the 3-formoxy group to hydroxy may becaused to occur, by extending the reaction period or by employingmorestrenuous reaction conditions. The conversion takes place under suchconditions, regardless of the acyloxy group at the 12 carbon atom, whichappears to be more stable. This is an important observation, allowingvariation of the nuclear acyloxy groups, as the S-hydroxyl may beacylated with a different group to produce a compound with unlikeacyloxy groups in the 3 and 12 positions.

Representative alcohols which may be prepared from the correspondingaldehydes by reduction with Raney nickel are as follows:

Alcohol 3-alpl1a-12-alpha-diacetoxy-23-hydroxy-nor-3-beta-acctoxy-24-hydroxy-(delta 5)-cholene 3-beta-24d1hydroxy- (delta5) -cholene 3-benzoxy-24-l1ydroxy-(delta 5) -cholene 182-1843-alpl1a-23-d1hydroxy-l2-alpha-acctoxy-!1or;cl1(plane- 17 2-1743-alpha-12-alpha-dlacetoxy-23-hydroxy-nor-cholene 148. 5-1513-beta-acetoxy-22-hydroiw- (delta 5) -bisnor-cholene 152-153. 5

The novel compounds of the present invention have the formula Otherrepresentative compounds, which may be prepared within the scope of thepresent invention are 31butyr0xy-24-hydroxy-cholane, 3formoxy-23-hydroxy-nor-cholane, 3-propionoxy-22-hydroxy-bisnorcholane,and 3-acetoxy-23-hydroxy-(delta 5) -norcholene.

Various modifications may be made in the present invention withoutdeparting from the spirit or scope thereof, and it is to be understoodthat we limit ourselves only as defined in the appended claims.

We claim:

1. The process which includes: converting a compound of the formula:

wherein P represents a nucleus selected from the group consisting ofpregnane, pregnene, and pregnadiene nuclei, which is attached to thesidechain in the 20 position; and n is selected from zero, one, and two;to a compound of the formula:

P-(CH2)1.--CH2OH wherein P and n have the previously assigned values, byreacting the steroid aldehyde with a Raney-type catalyst.

2. The process of claim 1, wherein the conversion is with Raney nickelin the presenceof an organic solvent.

3. The process which includes: transforming a steroid thioester into asteroid aldehyde and converting the aldehyde into a primary alcohol, byreacting the aldehyde with a Haney-type catalyst.

4. The process which includes: mixing a compound of the formula whereinP represents a nucleus selected from the group consisting of pregnane,pregnene, and pregnadiene nuclei, said nucleus having the sidechainattached in the 20 position; and n is selected from zero, one, and two;with a Raneytype catalyst at a temperature between about zero anddegrees centigrade; and separating a steroid alcohol of the formula:

wherein P and n have the values previously assigned, from the reactionproduct.

5. The process of claim 4, wherein the Raneytype composition is Raneynickel. "6. The process of claim 4, wherein the reaction is conductedwith Raney nickel in the presence of an organic solvent.

7. The process of claim 4, wherein the starting aldehyde is abisnor-(delta 5) -cholenal-22.

8. The process of claim 4, wherein the starting aldehyde is anor-cholanal-23.

9. The process of claim 4, wherein the starting aldehyde is a (delta 5)-cholenal-24.

ROBERT H. LEVIN. A. VERN MoINTOSH, JR. GEORGE B. SPERO.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,259,698 Johannessohn Oct. 21,1941 2,312,484 Reichstein Mar. 2, 1943

1. THE PROCESS WHICH INCLUDES: CONVERTING A COMPOUND OF THE FORMULA: